Role of Caveolin-1 in Indomethacin-induced Death of Human Hepato-adenocarcinoma SK-Hep1 Cells

  • Kim, Kyung-Nam (Department of Clinical Pharmacology, College of Medicine, Kyung Hee University, Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK21 Project) ;
  • Kang, Ju-Hee (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK21 Project, MTRC, Inha Research Institute for Medical Science, Inha University) ;
  • Yim, Sung-Vin (Department of Clinical Pharmacology, College of Medicine, Kyung Hee University) ;
  • Park, Chang-Shin (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK21 Project, MTRC, Inha Research Institute for Medical Science, Inha University)
  • Published : 2008.08.31

Abstract

Caveolin-1 (CAV1) is an integral membrane protein that may function as a scaffold for plasma membrane proteins and acts as a tumor suppressor protein. One causative factor of chemotherapy-resistant cancers is P-plycoprotein (P-gp), the product of the multidrug resistance-1 gene (MDR1), which is localized in the caveolar structure. Currently, the interactive roles of CAV1 and MDR1 expression in the death of cancer cells remain controversial. In this study, we investigated the effects of indomethacin on the cell viability and the expression levels of MDR1 mRNA and protein in a CAV1-siRNA-mediated gene knockdown hepatoma cell line (SK-Hep1). Cell viability was significantly decreased in CAV1-siRNA-transfected cells compared with that of control-siRNA-transfected cells. Furthermore, the viability of cells pretreated with CAV1 siRNA was markedly decreased by treatment with indomethacin (400${\mu}$M for 24 h). However, the protein and mRNA levels of MDR1 were unchanged in CAV1-siRNA-transfected cells. These results suggest that CAV1 plays an important role as a major survival enzyme in cancer cells, and indomethacin can sensitively induce cell death under conditions of reduced CAV1 expression, independent of MDR1 expression.

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